JPH0662467B2 - Alcohol production method - Google Patents

Description

Detailed Description of the Invention

[0001]

The present invention relates to the general formula [1] (In the formula, R ₁ represents a hydrogen atom, a C _1-6 linear or branched alkyl group or a phenyl group, and R ₂ represents a hydrogen atom or a methyl group.) Regarding The alcohols represented by the above general formula [1] are useful intermediates for agricultural chemicals, pharmaceuticals, fragrances and the like.

[0002]

As a method for producing an alcohol compound from a carbonyl compound or an oxirane compound, a method by a so-called Grignard reaction in which a Grignard reagent is prepared in advance and this is reacted with the carbonyl compound or the oxirane compound is known. It is common. As an example of this method, 3-Bromo-1-butyne and magnesium are prepared in ethyl ether using mercuric chloride as a catalyst to prepare a Grignard reagent, and this is reacted with a carbonyl compound [J. Org. Ghem ., Vol.
42, No. 11, 1960 (1977)], Propargyl bromide and magnesium in ethyl ether were used to prepare a Grignard reagent using mercuric chloride as a catalyst, and this was reacted with 5-methylfurfural (tetrahydrofuran solution). Methods (USP 3,892,782) and the like are known, but as seen in these methods, it was usually and best to use a mercury compound as a catalyst when preparing a Grignard reagent in such a reaction.

However, in these methods, the recovery of the mercury compound used as a catalyst is an important issue from the viewpoint of pollution. The production yield of the Grignard reagent is low unless a special device is used, so that a large amount of magnesium or propargyl halide is required, and the raw material cost becomes high. There are various drawbacks such as, and it is very disadvantageous as an industrial production method. As for the reaction method, a method of simultaneously reacting a halogenated propargyl compound and a carbonyl compound [JP-A-53-130618, J.Org.Chem., Vo
l.44, No.9, 1438 (1979)], but these methods also use a mercury compound as a catalyst,
No industrially advantageous manufacturing method has been found.

From the above, the present inventors have produced alcohols represented by the above general formula [1] in good yield without using a mercury compound as a catalyst and without using a special apparatus. As a result of extensive studies, the present invention has been achieved.

[0005]

That is, the present invention provides a general formula [2]. (Wherein R ₁ has the same meaning as described above), magnesium and the general formula (IV) (In the formula, X represents a halogen atom. R ₂ has the same meaning as described above.) After reacting the halogenated propargyls (first step), hydrolysis (second step), In producing the alcohol represented by the general formula [1], the reaction of the first step is carried out by reacting magnesium with an oxirane compound [2] and a propargyl halide in the presence of metallic zinc or zinc halide in an inert solvent. [3]
The present invention provides a method for producing alcohols represented by the above general formula [1], which is characterized in that and are simultaneously actuated.

The present invention will be described in detail below. Examples of the oxirane compound represented by the general formula [2] used in the present invention include ethylene oxide, propylene oxide,
Examples are butylene oxide and styrene oxide.

Examples of the halogenated propargyl compounds represented by the general formula [3] include propargyl chloride, propargyl bromide, 3-chloro-1-butyne and 3-bromo-1.
-Butyne and the like can be mentioned, and chloride and bromide can be optionally mixed and used. In the present invention, the use of zinc metal or zinc halide is extremely important as an activator replacing mercury compounds, and examples of the zinc halide include zinc chloride, zinc bromide and zinc iodide, which are mixed as a mixture. You may use. The amount of zinc metal or zinc halide used was 0. based on the starting oxirane compound [2].
The preferred range is from 05 mole times to 0.5 mole times, and the method of using it may be such that the entire amount thereof may be allowed to coexist in the reaction system from the beginning, or a part thereof may be used as the oxirane compound [2] and / or halogenated compound. It may be allowed to act together with propargyls [3].

Tetrahydrofuran (THF) used as an inert solvent is a suitable solvent for carrying out the present invention, and its amount used is preferably 2 times or more the weight of the starting oxirane compound [2], and the upper limit is The reaction is not particularly limited, but it is practically insignificant in terms of volume efficiency. This solvent may be used alone, but depending on the necessity of recovery and reuse of the solvent, another solvent inert to the reaction may be appropriately mixed and used. Examples of other inert solvents that can be mixed here include aromatic hydrocarbons such as benzene, toluene and xylene, and ether solvents such as tetrahydropyran, furan and dialkyl ether.

Simultaneous action of oxirane compound [2] and halogenated propargyls [3] on magnesium is an important requirement for achieving the object of the present invention, and a specific method therefor is the addition of magnesium as described above. There is a method in which an oxirane compound [2] and a propargyl halide [3] are separately and concurrently added to a solvent solution, or a mixture of the two is added continuously or intermittently. The mixture can be previously mixed with a solvent inert to the reaction.

In this way, when the oxirane compound [2] and the halogenated propargyl halides [3] are simultaneously acted on magnesium to add magnesium and halogenated propargyl halides [3] separately, both components are added. Does not have to be completely simultaneous addition, and can be continuously or intermittently added unless either one of the two components extremely precedes. The reaction temperature is preferably 10 to 60 ° C. If the temperature is too low, the reactivity becomes too low, and if the temperature is too high, the reactivity becomes too high, which is not desirable. The reaction pressure is not particularly limited, and when the reaction is performed under reduced pressure, heat removal by reflux and temperature control associated therewith are also possible.

In the method of the present invention, the amount of the propargyl halide [3] used with respect to the oxirane compound [2] is usually 1.05 to 1.5 mol times, and preferably 1.1 to 1.3 mol times. The amount used is preferably 1.05 mol times or more, and the upper limit is not particularly limited. In carrying out the Grignard reaction in the present invention, a small amount of magnesium is present in the presence of metallic zinc or zinc halide before the oxirane compounds [2] and the propargyl halide [3] are simultaneously allowed to act on magnesium. It is preferable to pre-treat with the halogenated propargyl halide [3].

The Grignard reaction product thus obtained is hydrolyzed to give the desired alcohols [1]. The conditions of this hydrolysis are not particularly limited, and can be easily hydrolyzed by an ordinary method using an aqueous solution of a mineral acid such as ammonium chloride, hydrochloric acid or sulfuric acid, an organic acid such as acetic acid or a mixed solution thereof. The hydrolysis reaction product can be purified by distillation or the like, if necessary.

Thus, according to the method of the present invention, the alcohols represented by the general formula [1] can be obtained in good yield and industrially very advantageously.

[0014]

EXAMPLES The present invention will be described in detail below with reference to examples. Example 1 A dried and nitrogen-purged 500 ml round-bottomed flask was charged with 18.2 g of granular magnesium, 10.2 g of dried zinc chloride and 100 g of dried tetrahydrofuran and stirred for 10 hours.
Add 0.88 g of propargyl bromide at ℃ and keep it adiabatic. When the reaction started and the heat generation stopped, a mixed solution of 29.0 g of propylene oxide, 74.3 g of propargyl bromide and 125 g of tetrahydrofuran was added dropwise at 40 ° C. over 0.5 hours while cooling with stirring, and then It was kept under stirring at room temperature for 30 minutes. After completion of the reaction, this reaction solution and 1.82
225 g of a mixed aqueous solution containing 1% by weight of acetic acid and 13.6% by weight of sulfuric acid was added to 250 g of water with stirring at 30 ° C. or lower, p
It was co-injected with H4 or more over 20 minutes, and then kept under stirring at room temperature for 30 minutes. After the reaction was completed, the reaction solution was separated and the aqueous layer was separated. The oil layer was washed with a 5 wt% sodium carbonate aqueous solution, and then the solvent was distilled off, followed by vacuum distillation (55 to 58 ° C).
/ 15mmHg) and then 5-hydroxy-1-hexyne 36.1g
Got The yield based on propylene oxide was 70%.

Claims (5)

[Claims] 1. A general formula [2] (In the formula, R ₁ represents a hydrogen atom, a C _1-6 linear or branched alkyl group or a phenyl group.), Magnesium and the general formula [3]. (In the formula, R ₂ represents a hydrogen atom or a methyl group, and X represents a halogen atom.) After reacting with halogenated propargyls (first step), hydrolysis (second step)
Then, the general formula [1] (In the formula, R ₁ and R ₂ have the same meanings as described above.)
In the production of the alcohols represented by the formula 1, the reaction of the first step is carried out by simultaneously treating the magnesium with the oxirane compound [2] and the propargyl halide [3] in the presence of metallic zinc or zinc halide in an inert solvent. The method for producing alcohols represented by the above general formula [1], which is characterized in that the alcohols are reacted with each other. 2. The method according to claim 1, wherein the inert solvent is tetrahydrofuran. 3. The method according to claim 1, wherein the zinc halide is one or more selected from zinc chloride, zinc bromide and zinc iodide. 4. The method according to claim 1, wherein the amount of zinc metal or zinc halide used is 0.05 to 0.5 mol times that of the oxirane compound [2]. 5. The method according to claim 1, wherein the halogen atom of the propargyl halide [3] is a bromine atom or a chlorine atom.